Zhengang Yu, G. Guo, Bingzhe Wang
Sep 1, 2020
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Journal of B.U.ON. : official journal of the Balkan Union of Oncology
Abstract
PURPOSE Lycopsamine is an active pyrrolizidine alkaloid that shows significant bioactivity. Herein, lycopsamine was evaluated for the first time for its anti-lung cancer activity. Its effects on cellular apoptosis, autophagy, cell cycle and IL-2 gene were also examined. METHODS The human lung cancer A549 and normal MRC5 cells were used in the study. MTT assay was used to determine the cytotoxicity of lycopsamine. Transmission electron microscopy (TEM) and western blotting were implemented for analyzing autophagy. DAPI staining, Annexin V/FITC/Propidium iodide (PI) and western blotting assays were used to study cellular apoptosis. Cell cycle was examined through flow cytometry. The expression of IL-2 gene was monitored by western blotting. RESULTS Lycopsamine targeted the proliferation rate and reduced it remarkably in a dose-dependent manner. On searching for underlying mechanism, the antiproliferative effect of lycopsamine was due to autophagy and the expressions of pro-autophagy proteins (LC3-I, LC3-II, Beclin-1) increased on drug exposure. Furthermore, the antiproliferative effects were also found to be mediated via apoptosis induction and were associated with increased Bax and decreased Bcl-2 levels. Next, flow cytometry showed that lycopsamine inhibited cell cycle progression at G2/M-check point in lung cancer cells. Furthermore, the expressions of IL-2 gene decreased after lycopsamine treatment of these cells. In conclusion, on testifying the current designed hypothesis, lycopsamine showed significant antiproliferative effects in A549 lung cancer cells in a dose reliant manner. The antiproliferative effects of lycopsamine were associated with its autophagy inducing, apoptosis inducing, and inhibiting IL-2 expression, potential. CONCLUSION Taken together, lycopsamine is a potent anti-lung cancer agent and can be a lead molecule in lung cancer treatment.